Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Disease, Pregnancy Related, Type 1 Diabetes Mellitus
Conditions
Keywords
Type 1 diabetes, pregnancy, closed-loop, clinical trial
Brief summary
This trial will assess the efficacy of the Tandem t:slim X2 insulin pump with Control IQ technology compared with standard insulin delivery plus CGM in pregnant women with type 1 diabetes.
Detailed description
Pregnant women with type 1 diabetes (T1D) require normal or near normal glucose in order to reduce the risks of birth defects, stillbirth, increased birthweight, neonatal hypoglycemia, neonatal death, preterm delivery and preeclampsia. Reducing maternal glucose is extremely difficult due to an increased risk of maternal hypoglycemia. Only 14% of T1D pregnancies achieve pregnancy guideline recommended glucose control, leading to complications related to high maternal glucose exposure in roughly half of newborns. Maintaining recommended maternal glucose levels during pregnancy reduces the risk of adverse neonatal outcomes to those similar in pregnancies unaffected by T1D. Most insulin pumps in use today are open-loop systems, which means that the user must program the pump to deliver a pre-set amount of insulin. These insulin delivery methods (MDI and open-loop pumps) are usually inadequate to achieve the optimal glucose control necessary for T1D pregnancies and they impart a large time, effort and emotional burden. Closed-loop systems have been found to be effective in improving glucose control outside of pregnancy when studied in children and adults. A new hybrid closed-loop system, the Tandem t:slim X2 insulin pump with Control IQ technology, recently became commercially available. Trials have demonstrated the efficacy of the Control IQ algorithm for non-pregnant adults and children. Pregnant women were not included in these trials. The investigators propose the first randomized controlled trial to evaluate the Tandem t:slim X2 insulin pump with Control IQ technology versus standard insulin delivery (MDI or pump) and CGM in pregnant women with T1D. In this trial, the investigators will assess the efficacy of the Tandem t:slim X2 insulin pump with Control IQ technology compared with standard insulin delivery plus CGM in pregnant women with type 1 diabetes. We are grateful to Tandem Diabetes Care and Dexcom for in-kind donations to this investigator initiated study.
Interventions
DEVICETandem t:slim X2 insulin pump with Control IQ technology
The intervention group will be fitted with the Tandem t:slim X2 insulin pump with Control IQ technology during pregnancy.
Sponsors
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Between 18 and 45 years of age (inclusive) * A diagnosis of type 1 diabetes, as defined by Diabetes Canada, for at least 12 months * A viable singleton pregnancy confirmed by ultrasound, less than 14 weeks gestation * Currently on intensive insulin therapy (≥ 3 injections, or Continuous subcutaneous insulin infusion (CSII) * Willingness to use the study devices throughout the trial * A1c ≥ 6.2% and \<10% measured any time during pregnancy prior to enrollment * Able to provide informed consent * Have access to email
Exclusion criteria
* Non-type 1 diabetes * Current treatment with drugs known to interfere with glucose metabolism as judged by the investigator such as high dose systemic corticosteroids * Known or suspected allergy to insulin * Women with nephropathy (estimated glomerular filtration rate \[eGFR\] \<45), severe autonomic neuropathy, uncontrolled gastroparesis or severe proliferative retinopathy, as judged by the investigator, that is likely to interfere with the normal conduct of the study and interpretation of study results * Total daily insulin dose \<8 or \>250 units/day at screening * Severe visual or hearing impairment, as judged by the investigator to impact treatment compliance * Unable to communicate effectively in English or French as judged by the investigator * Current use of Tandem Control IQ, DIY looping system, 670G in Auto Mode, or alternate closed-loop system as judged by the investigator * Any reason judged by the investigator that would likely interfere with the normal conduct of the study and interpretation of study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic control as reflected by percent glucose time-in-range | 16 weeks until 34 weeks gestation | Time in range (3.5 to 7.8 mmol/L) per day assessed by CGM glucose measurement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent time spent below target range per day (+/-SD) | 16 weeks gestation until delivery of neonate | Glucose below target range defined as glucose \< 3.5 mmol/L; Blood glucose will be assessed using CGM data |
| Mean blood glucose measurement at 24 and 34 weeks (+/-SD) | 24 and 34 weeks gestation | Blood glucose measured in mmol/L and assessed using CGM data |
| Proportion of participants who experience maternal hypoglycemic events | 16 weeks gestation until delivery of neonate | Maternal hypoglycemic events defined as ≥15 minutes with CGM glucose \<3.5 mmol/L \[level 1\] or \<2.8 mmol/L \[level 2\]; Blood glucose will be assessed using CGM data |
| Glycemic variability reflected by the coefficients of variation and standard deviations of CGM data | 16 weeks gestation until delivery of neonate | Blood glucose measured in mmol/L and assessed using CGM data |
| Diabetes-related distress to the participant | 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum | Diabetes-related distress will be assessed four times during the study using the Diabetes Distress Screening Scale (DDSS17) |
| Fear of hypoglycemia | 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum | Fear of hypoglycemia will be assessed four times during the study using the Hypoglycemia Fear Survey Questionnaire II (HFSQ II) |
| Fear of hyperglycemia | 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum | Fear of hyperglycemia will be assessed four times during the study using the g. Hyperglycemia Fear in Pregnancy Survey |
| Sleep quality | 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum | Sleep quality will be assessed at four times during the study using the Modified Pittsburgh Sleep Quality Index (PSQI) |
| Health-related quality of life | 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum | Health-related quality of life will be assessed four times during the study using the Euro Quality of life questionnaire (EQ-5D-5L) |
| Work productivity | 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum | Work productivity will be assessed four times during the study using the Work Productivity and Activity Impairment survey |
| Diabetes-related distress to the partners | 7-13 weeks + 6 days gestation, 24 weeks gestation, 34 weeks gestation, 6 weeks postpartum | Diabetes-related distress to the partners will be assessed four times during the study using the Partner Diabetes Distress Scale |
| Proportion of participants who experience preeclampsia events | 16 weeks gestation until delivery of neonate | Preeclampsia is defined as pregnancy ≥20 wks gestation with SBP ≥140mmHg and/or DBP ≥90 mmHg on ≥2 occasions a minimum of 6 hrs apart and new-onset of proteinuria (defined as urinary excretion ≥0.3g protein on a 24-hr urine specimen, or ≥ 2+ by urinary dipstick, or ≥30mg protein/mmol of urinary creatinine by spot testing) OR ≥1 of the following adverse conditions: * Eclampsia (Seizures in pregnancy) * Elevated liver function tests (Increased AST and/or ALT \>70 IU/L) * Decreased platelet count \<100 x 109/L * Elevated serum creatinine (\>80 μmol/L) * Small for gestational age infant (birth weight \<10th percentile) |
| Proportion of participants who experience gestational hypertension events | 16 weeks gestation until delivery of neonate | Gestational hypertension is defined as a woman ≥20 weeks gestation with a systolic blood pressure of ≥140 mm Hg and/or a diastolic blood pressure ≥90 mm Hg on ≥2 occasions a minimum of 6 hours apart without proteinuria |
| Percent time spent above target range per day (+/-SD) | 16 weeks gestation until delivery of neonate | Glucose above target range defined as glucose \>7.8 mmol/L; Blood glucose will be assessed using CGM data |
| Proportion of participants who have caesarean deliveries | 16 weeks gestation until delivery of neonate | — |
| Proportion of participants who experience preterm births | Delivery of neonate to 6 weeks postpartum | Preterm birth defined as birth occurring \<37 weeks gestation |
| Proportion of babies born large for gestational age (>90th percentile) | Delivery of neonate | — |
| Proportion of babies born small for gestational age (<10th percentile) | Delivery of neonate | — |
| Mean neonatal birthweight (+/-SD) | Delivery of neonate | Birthweight measured in kilograms |
| Comparison of birthweight z-score | Delivery of neonate | — |
| Proportion of babies born with neonatal hypoglycemia | Delivery of neonate | — |
| Proportion of neonates admitted to intensive care unit admission | Delivery of neonate to 6 weeks postpartum | Admission to neonatal intensive care unit admission defined as admission of 24 hours or more |
| Proportion of participants who experienced pregnancy loss or miscarriage (< 20 weeks, stillbirth ≥20 weeks, neonatal loss up to 28 days) | 7-13 weeks until delivery of neonate + up to 28 days | — |
| Proportion of participants who experience episodes of severe hypoglycemia | 7-13 weeks + 6 days gestation until delivery of neonate | Severe hypoglycemia defined as a hypoglycemic episode requiring assistance from another person. |
| Proportion of participants who experience episodes of diabetic ketoacidosis | 7-13 weeks + 6 days gestation until delivery of neonate | Diabetic ketoacidosis (DKA) is defined as an episode with elevated plasma ketones which can be categorized as possible DKA (mild/ self- treated \[plasma ketones 0.6 - 1.5mmol/L\], moderate/self-treated (plasma ketones \> 1.5mmol/L which resolves without hospital admission), or capillary blood ketones \>3.0 mol/L without an anion gap of \> 15 with admission to hospital for another reason \[i.e. prevention of DKA\]) or confirmed DKA (severe, with either plasma ketones \> 3.0mmol/L or positive serum ketones with an anion gap (Na -(CI+HC03) \> 15 and requiring hospital admission for IV fluids and IV insulin to correct the abnormal metabolic state). |
| Proportion of participants who experience device-related adverse events | 7-13 weeks + 6 days gestation until delivery of neonate | Device-related adverse events include skin reactions and insulin delivery failures. |
| Proportion of participants who experience worsening chronic hypertension events | 16 weeks gestation until delivery of neonate | Chronic hypertension is defined as hypertension that is present at \<20 weeks gestation or pre-pregnancy |
Countries
Australia, Canada
Outcome results
None listed